Gas sensor

ABSTRACT

We describe a method of selectively detecting the presence of an analyte. The method comprises providing a waveguide with a core comprising porous material; absorbing an analyte sample into the porous material of the core such that the analyte sample is held within pores of the core; waveguiding radiation along the waveguide to an output; measuring spectral features of the output radiation due to absorption or scattering of said waveguided radiation by the absorbed analyte sample; and selectively identifying the presence of a target analyte in the sample from the spectral features. In embodiments spectral features are measured for multiple different waveguide core regions having different physical/chemical properties modified to provide additional selectivity to the target analyte(s), and these measurements are combined to identify the target analyte.

FIELD OF THE INVENTION

This invention relates to methods and apparatus for selectivelydetecting the presence of an analyte, in particular a gas (vapour), andto methods of fabricating sensors for such methods/apparatus.

BACKGROUND TO THE INVENTION

Many sensors based on porous silicon have been reported, and some useporous silicon waveguides. In particular we have previously describedsensors which measure the change in refractive index of a porouswaveguide: Tanya Hutter, Nikos Bamiedakis and Stephen Elliott,“Theoretical Study of Porous Silicon Waveguides and Their Applicabilityfor Vapour Sensing”, Proceedings of the COMSOL Conference 2010 Paris,2010; Tanya Hutter, Stephen R. Elliott and Shlomo Ruschin, Dynamic RangeEnhancement and Phase-Ambiguity Elimination in Wavelength-InterrogatedInterferometer Sensor, Sensors and Actuators B, 178, 593-597, 2013.Other work on porous silicon waveguides for biosensing can be found inL. Haji et al (2012). However these approaches rely on interferencetechniques to measure the change in refractive index of porous silicon,which limits their selectivity. By contrast, typical waveguide-basedsensors provide the target material on an outer surface of the waveguideand rely on the interaction of an evanescent wave (of light propagatingwithin the waveguide) with the analyte, which has limited sensitivity.

Other background prior art can be found in: EP0979994, EP2108944,US2012/0327398, U.S. Pat. No. 8,617,471, US2013/0081447, EP2108944, U.S.Pat. No. 8,636,955, WO2011/140156, WO2011/107868, JP2011/075513,EP2115428, US2009/059234, FR2856150, U.S. Pat. No. 6,375,725, andWO01/94915.

As noted, the above described techniques suffer from various problemsincluding a lack of specificity and sensitivity.

SUMMARY OF THE INVENTION

According to the present invention there is therefore provided a methodof selectively detecting the presence of an analyte, the methodcomprising: providing at least one waveguide, the waveguide having anoptical core comprising porous material; absorbing an analyte sampleinto said porous material of said core such that said analyte sample isheld within pores of said core; waveguiding radiation along said atleast one waveguide to an output to provide output radiation; measuringone or more spectral features of said output radiation due to absorptionor scattering of said waveguided radiation by said absorbed analytesample; selectively identifying the presence of a target analyte in saidanalyte sample from said one or more spectral features.

In some preferred embodiments the radiation comprises optical radiationof any suitable wavelength or range of wavelengths including, but notlimited to: ultraviolet, visible, near and far infrared; this may bedelivered to the wave guide for example via a fibre optic. In principle,however, radiation of other wavelengths such as terahertz radiation mayalso be employed. By absorbing the analyte, typically a gas (vapour)into the porous material of the core the waveguide structure enablesabsorption spectroscopy to be performed on the analyte sample with agreater signal than is provided by other approaches. Thus in embodimentsof the method the measured spectral features of the output radiation aredue to one or more inherent properties of the absorbed analyte sample.In embodiments the porous material may contain substantially only theanalysed material (and functionalising material, if used).

Preferably the absorption spectrum of the absorbed analyte isinterrogated, but in principle other forms of spectroscopy such asscattering or Raman spectroscopy may additionally or alternatively beemployed. Thus in embodiments the one or more spectral featuresidentified by the method comprise features at absorption wavelengthpeaks/troughs of the analyte(s), or in principle features at scattering(Raman) peaks. The method may be used to selectively identify thepresence of one or more target analytes, for example a mixture of gases.In embodiments the measuring of the one or more spectral features maysimply comprise comparison with a threshold to identify whether or not atarget analyte is present in the sample.

The use of a waveguide with a porous, at least partially exposed coreprovides additional opportunities for selective detection of one or moretargets. (As the skilled person will know, the (optical) core of awaveguide is the region of the waveguide in which light propagates whentravelling through the waveguide). Such an approach also enablesselective exclusion of one or more chemical compounds from the core. Inbroad terms, the pore size of pores in the waveguide may be tuned toselectively exclude larger molecules. More generally, embodiments of themethod employ a plurality of different core regions modified indifferent ways, either physically and/or chemically, to provideadditional selectivity to the target analyte or analytes. The differentcore regions may be different parts of the same waveguide and/or may beparts of different waveguides—for example in embodiments an array ofwaveguides may be employed with a set of different pore sizes and/orsurface modifications.

One difficulty with, for example, NIR spectroscopy is that it can bedifficult to distinguish between certain different types of molecule.For example an OH absorption band is seen for both water and methanol;and in a long chain hydrocarbon or fatty acid it can be difficult todistinguish the length of the chain. In embodiments of the method,therefore, a set of different core regions is provided each with adifferent pore size distribution—that is with pore size distributionshaving peaks at different pore sizes. The pore size may be measured byany convenient technique; the skilled person will appreciate thatdepending upon the measurement technique (see later) what is beingmeasured may not exactly correspond to a physical core dimension at asurface of the core of the waveguide. However in embodiments of themethod the particular precise pore size may not be important providedthat a set of different pore sizes is employed, providing somedifferentiation between one or more target molecules and the background.The skilled person will also appreciate that, broadly speaking, largerpores are associated with greater porosity (i.e. a greater percentage ofunoccupied space in the porous ‘sponge’), and thus porosity may beemployed as a proxy for pore size in some situations. Preferably thewaveguide core comprises a mostly open pore network (internal pores havea pathway to the external core surface), rather than a mostly closedpore network, to facilitate absorption of the analyte, though this isnot essential. (Pores produced in silicon by the electrochemical methoddescribed later are mostly open).

Additionally or alternatively one or more core regions of the one ormore waveguides may be derivatized or functionalised, for example bytreating the core material so that an internal surface of the pores isat least partially coated with a molecular material, in particular onewhich changes an affinity of the core waveguide material for the targetanalyte or analytes. Thus an internal surface of the pores may beprovided with one or more different functional groups. The skilledperson will be aware of many such functional groups which may beprovided including, but not limited to: CH₃, CN, COOH, NH₂, and longeralkyl chains. The skilled person will also be aware of many suchfunctionalising techniques including techniques based on smallmolecules, polymers, and self-assembled layers such as self-assembledmonolayers (see, for example, U.S. Pat. No. 6,518,205, WO2002/079085,and WO2000/026019). Functionalising the pores in the core mayadditionally or alternatively comprise a physical treatment such asplasma treatment. Thus the waveguide core may be functionalised with asmall molecule or polymer ligand, such as a hydrophilic or hydrophobicligand, and/or a ligand having functional groups such as alcohol (—OH),aldehyde (—COH), amide (—CON), carboxylic acid (—COOH), methyl (—CH₃) orthe like. A more complex functionalising material may also be employed,for example a biologically active molecule or peptide/protein such asDNA, RNA, or an antibody. For example these may be covalently coupled toa functionalised or native silicon/oxide surface.

Where multiple core regions with different properties are provided themultiple signals from such regions may be analysed using multi-componentanalysis, such as principle component analysis or one of the manysimilar techniques, to more accurately/selectively identify the presenceof one or more targets.

Additionally or alternatively further selectivity/specificity may beachieved by operating at two or more different temperatures: both thephysical and chemical interactions of a target with the porous corematerial are temperature dependent. Thus by operating at more than onetemperature a further parameter is obtained which can be used todistinguish between targets and/or distinguish a target from thebackground. In broad terms, operating at multiple temperatures enablestargets to be distinguished based upon their intrinsic properties inaddition to their absorption spectrum. This can facilitatedifferentiating between, for example, long and short chain molecules. Ina functionalised device binding of a target is temperature-dependent andchanging temperature may be used for increased selectivity. In addition,the time dependent sensor signal (transient response) provides furtherdiscrimination between analytes.

More particularly, depending upon the temperature and other parameterssuch as pore size/shape, a target material may become liquid in thepores at certain vapour concentrations and certain temperatures. Thusthe operating temperatures may be selected to change a degree of vapourcondensation of the target within the pores. As well as providingadditional selectivity depending upon the temperatures chosen,interrogating a condensed material in the gaseous and liquid phasegenerates different types of spectroscopic data—for example anabsorption peak may vary in width. More generally, however, thetemperature change may simply change the degree of analyte adsorption bythe surfaces of the pores without actually condensing the vapour.

In some embodiments of the method the condensation kinetics of a gas areinvestigated by changing a temperature, to differentiate betweendifferent vapours which condense at different rates and to a differentextent. The skilled person will appreciate that one waveguide may beoperated at multiple different temperatures, changing the temperature ofthe waveguide in time and/or space (along the waveguide) and/or multipledifferent waveguides may be employed operating at multiple differenttemperatures.

In some embodiments of the method light of a single wavelength, forexample from the light emitting diode or laser is waveguided tointerrogate a particular target absorption (or scattering) peak ortrough. In other approaches multiple substantially discrete wavelengthsare employed, or broadband radiation may be employed, to measure anabsorption (or scattering) spectrum. In particular, embodiments of themethod measure an absorption (or scattering) spectrum of an analyteabsorbed within the waveguide.

In embodiments the measured spectrum or interrogated wavelengths arecharacteristic of the analytes(s) under investigation rather thancharacteristic of the waveguide—that is the spectrum or wavelength(s)comprise an absorption (or scattering) spectrum or wavelength(s) of theanalyte(s).

Depending upon how the waveguide is made, the pores may not have awell-defined size—for example where porous silicon is employed a surfaceof the silicon may have approximately regular pores whilst avertical-cross section through the material may reveal a morefractal-like structure. Nonetheless it is possible to measure a poresize distribution and determine an average pore size, in particular atan outer surface of the core of the waveguide, as described later. Whenpore size is measured in this way the pores have a size distributionwith a peak at less than 500 nm; or less than 400 nm, 300 nm, 200 nm,100 nm or 50 nm. Alternatively the pore size may be specified as a mean,medium, mode or maximum dimension or pitch less than 500 nm; or lessthan 400 nm, 300 nm, 200 nm, 100 nm or 50 nm.

In embodiments the pores of the optical core may be substantially randomor may have some (or substantially complete) regularity. For example inembodiments they may define an interconnected network; and/or they may,for example, define longitudinal passages. Whatever the change of thepores the light propagation through the pores themselves (rather than,say, through a region bounded by the pores). Where the pores have agenerally longitudinal shape, the longitudinal axis may be alignedperpendicular to the direction of light propagation through the porousoptical core.

In preferred embodiments of the method the pores are significantlysmaller than a wavelength of the waveguided radiation, to reducescattering losses in the waveguide. When measured at a surface of thecore of porous material the pores may have an average minimum lateraldimension (measured on the surface) of less than 500 nm, 400 nm, 300 nm,200 nm, 100 nm or 50 nm; or, for example, an average minimum lateraldimension at least two or preferably ten times smaller than a wavelengthof the waveguided radiation.

If the average pore size (the average ‘diameter’ of a pore which extendslongitudinally) in less than the wavelength(s) of light used then theporous material will be substantially transparent, or at least havereduced attenuation. In broad terms the light propagating through theporous material should not “see” a significant propagation (say morethan 20%) of structure having a size greater than the wavelength(s).

Many different approaches may be employed to fabricate the porous coreof the waveguide. These include, but are not limited to: electrochemicaletching of semiconductors; a sol-gel process; nanoparticle self-assemblyprocess; and use of porous alumina or porous polymers. In embodiments,however, the waveguide is fabricated on a substrate using porous siliconfor the core (which may be oxidised to porous silica). Conveniently thesubstrate is silicon, although this is not essential as such a waveguidemay be fabricated on silicon and afterwards lifted off.

In one approach the core material is separated from the underlying(silicon) substrate by a region of ‘cladding’, the cladding having alower refractive index than the core (so that the core is separated fromthe higher refractive index silicon, to enable the waveguiding). Inother approaches, however, the cladding is optional—for example asuitable waveguide may be fabricated from a layer of titanium dioxide(nano)particles which may be deposited directly on a non-poroussubstrate of lower refractive index, such as a silica surface. Thus inembodiments the core of a waveguide may be partially or completelysurrounded by cladding (apart from a region exposing the core togas/vapour), but this is not essential. Where cladding is present, itmay be non-porous.

The skilled person will appreciate that in embodiments a substrate forthe waveguide is not essential. It is useful in a layered structure, butin other arrangements the core (and optional cladding) may be suspendedbetween supports, as illustrated schematically in FIG. 4c . Thisapproach is particularly suitable for a fibre-type core but may also beused to support a slab of waveguide material (core with or withoutcladding). Supporting a waveguide comprising a porous core with an airor gas cladding is advantageous because it facilitates access of analyteto the porous material of the core. Thus in some approaches the corematerial may be separate from any substrate such that the surroundingenvironment, such as air, acts as a lower refractive index medium. Thisarrangement facilitates absorption of analytes into the core through theentire outer surface in a lateral direction.

In one approach a waveguide may be fabricated buried within the surfaceof a silicon substrate, by etching respective cladding and core layersinto the surface of the silicon. In another, preferred approach howevera waveguiding structure is supported on the surface of a siliconsubstrate.

Thus in a related aspect the invention provides a method of fabricatinga waveguide for an analyte sensor as described above, the methodcomprising: providing a silicon substrate; supplying a first current ata first current density perpendicular to said substrate; performing afirst etch of said substrate to fabricate said core layer; and supplyinga second current at a second density slowly perpendicular to saidsubstrate; performing a second etch of said substrate to fabricate saidcore layer.

Broadly speaking by applying a current in a vertical direction through asilicon substrate and then etching the substrate, for example usinghydrofluoric acid, a porous layer can be grown down into the substrate.The current density determines the porosity. In this way a layeredstructure can be fabricated in which a core layer is disposed on aslightly more porous cladding layer of lower refractive index, which isin turn disposed on the underlying (silicon) substrate. Lateral edges ofthe core defining the waveguide may be formed either before or after theetching. The structure may then be provided with fibre optic input andoutput connections for waveguiding light through the structure.

In a related aspect the invention provides an analyte sensor, the sensorcomprising: a substrate bearing a waveguide, the waveguide comprising: afirst, cladding layer on said substrate; a second, (optical) core layer,comprising porous material, over said cladding layer; a radiation sourceto provide radiation into said waveguide; a radiation detector to detectradiation which has been waveguided along said waveguide; and a signalprocessor, coupled to said radiation detector, to identify the presenceof a target analyte absorbed within said core layer from one or morespectral features of said detected radiation due to absorption orscattering of said waveguided radiation by said absorbed target analyte.

In embodiments of the above described sensor/method, an analyte fittermay be located above the core, in particular as an additional layer overthe core (when it should have a lower refractive index than the core).For example, such a filter may comprise an additional layer of poroussilicon over the core, optionally functionalised.

In a further related aspect the invention provides apparatus forselectively detecting the presence of an analyte, the apparatuscomprising: at least one waveguide, the waveguide having (an optical)core comprising porous material; a radiation source to provide radiationinto said waveguide; a radiation detector to detect radiation which hasbeen waveguided along said waveguide; and a signal processor, coupled tosaid radiation detector, to identify the presence of a target analyteabsorbed within said core layer from one or more spectral features ofsaid detected radiation due to absorption or scattering of saidwaveguided radiation by said absorbed target analyte.

Corresponding features to those previously described may be provided inembodiments of the apparatus. Thus, for example, the signal processormay be configured to process signals from a plurality of core regions ofthe waveguide physically and/or chemically modified to be different toone another, to enhance the selectivity of the apparatus. Additionallyor alternatively a temperature controller may be employed to operate oneor more waveguides or portions of waveguides at different temperatures.

The skilled person will appreciate that the signal processor processingthe signal from the radiation detector may comprise analogue or digitalelectronics and/or a processor, such as a digital signal processor orgeneral purpose computer, operating under control of stored processorcontrol code.

Embodiments of the above described methods and apparatus have manyapplications including, but not limited to: Detection of analytes thatare toxic to human health and/or degrade air quality; detection ofanalytes in industrial chemical processes and reaction chambers;detection of analytes that constitute an explosive risk; detection ofanalytes that are associated with the detection of drugs/illegalsubstances; detection of analytes contained within human or animalbodily fluids (including for example exhaled breath, urine, blood,sputum); and detection of analytes from human or animal cell gasexchange.

One useful application is in analysing a urine sample, in particular toprovide information on patient kidney function. The techniques wedescribe above are able to provide information which is difficult orimpossible to obtain conveniently by other techniques. In particular thetechniques we describe provide a sensitive, low cost method of obtainingan absorption spectrum of one or more, volatile organic compounds (VOCs)from the sample, especially VOCs associated with diseases such as kidneydisease and cancers, such as colon cancer and prostate cancer.

In one embodiment apparatus for this purpose includes sensor apparatusas previously described, together with a urine sample holder and ashutter to selectively allow passage of urine vapour from the sampleholder to the sensor for analysis.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other aspects of the invention will now be further described,by way of example only, with reference to the accompanying figures inwhich:

FIG. 1 shows a schematic illustration of three different waveguide typesand their interactions with molecules, showing (a) a conventionalwaveguide, (b) a slot-waveguide and (c) a porous waveguide according toan embodiment of the invention; the target analyte molecules arerepresented as dots and the diffuse circles represent the propagatingmode;

FIG. 2 illustrates absorption of light by molecules, showing that forthe same physical interaction length, a nanoporous waveguide (lowerfigure; dispersed molecules, small interaction length, small absorptionpeak) provides significantly higher effective interaction length thanwith a gas (upper figure; molecules condensed within the material of thewaveguide core, large effective interaction length, strong absorptionpeak), thus increasing the sensitivity of detection;

FIG. 3 shows the dynamic response of a single porous silicon layer forhexane vapour (left) and ethyl acetate vapour (right) at variousconcentrations, showing a measure of physical absorption of the vapourby the porous silicon on the y-axis;

FIGS. 4a to 4c show, respectively, the structure of an examplefabricated PSi (porous silicon) waveguide comprising a porous core layeron a cladding layer, with inset HR-SEM (high resolution scanningelectron microscope) images of the top surface and a cross-section viewof the pore morphology (the scale bars are 100 nm); a first variantwaveguide structure; and second variant waveguide structure withoutsubstrate or cladding;

FIG. 5 shows a vertical cross-section of a porous waveguide array(individual waveguides indicated with arrows), showing the emitted lightfrom two adjacent waveguides (FIGS. 5a, 5b ), and light propagationalong a waveguide (FIG. 5c );

FIG. 6 shows, schematically, experimental apparatus used to characterisea sensor according to an embodiment of the invention;

FIGS. 7a to 7d show example measured spectra from the apparatus of FIG.6 for, respectively, pentane, methanol, acetone and isopropyl alcohol;

FIGS. 8a to 8d show analyte sensing systems according to embodiments ofthe invention;

FIG. 9 shows a vertical cross-section through a temperature controlledporous waveguide sensor according to an embodiment of the invention; and

FIG. 10 shows an example of an analyte sensing probe comprising a porouswaveguide according to an embodiment of the invention.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

We will describe techniques for optical spectroscopy of analytes in thepores of a porous waveguide. Some initial background material is helpfulfor understanding the invention:

Spectroscopy

Optical absorption spectroscopy is based on illuminating a chemicalcompound with a light and measuring the light absorption as a result ofa presence of that chemical compound. Different molecules absorb lightof different wavelengths. An absorption spectrum will show a number ofabsorption bands corresponding to structural groups within the molecule.

Absorbance is directly proportional to the path length, b, and theconcentration, c, of the absorbing species. Beer's Law states thatA=cbc, where £ is a constant of proportionality, called theabsorbtivity.

The radiation can be of any wavelength ranging from the UV to IR andeven THz.

Porous Silicon

Porous silicon is typically fabricated using electrochemical etching.The porosity of the fabricated layer depends on several parameters(wafer doping, temp, solution) and the applied current density duringthe electrochemical etching. The refractive index of a porous layerdepends on the porosity, and therefore can be easily controlled. Thisenables easy fabrication of optical components such as Bragg reflectors,multilayers structures and waveguides.

In addition, the porous nature of the material can be used to host otheroptical materials, nanoparticles, chemical molecules and dyes.

Waveguides

An optical waveguide is a physical structure that guides electromagneticwaves, i.e. the electromagnetic waves propagate within the boundaries ofthe structure. Optical waveguides can be classified according to theirgeometry (planar, strip, or fibre waveguides), mode structure(single-mode, multi-mode), refractive index distribution (step orgradient index) and material (glass, polymer, semiconductor). As theskilled person will appreciate, a waveguide generally comprises a corewith a cladding (which may be gas/air/vacuum) of lower refractive index.

Capillary Condensation

The number of molecules that can be adsorbed by a porous layer islimited by the total pore volume. The pores' curved surfaces enhance theattraction for molecules of wetting substances due to van der Waalsinteractions, resulting in adsorption and capillary condensation.Capillary condensation is the physical tendency for a vapour to condensein a small pore at temperatures well above the dew point, and isdescribed by the Kelvin equation:

${N_{A}{kT}\; {\ln \left( \frac{P}{P_{0}} \right)}} = {- \frac{2\; M\; \gamma \; \cos \; \theta}{r\; \rho}}$

where N_(A) is Avogadro's constant, k is the Boltzmann constant, T isthe absolute temperature, M is the molecular weight, ρ is the liquiddensity, r is the radius of the capillary, θ is the contact angle, γ isthe surface tension, P₀ is the saturation pressure and P is theequilibrium vapour pressure. Therefore, the smaller the pore radius, thelower is the relative vapour pressure at which capillary-condensationcan occur at a given temperature. During the capillary-condensationprocess, the air in the voids is replaced by condensed vapour. Theextent of both the monolayer adsorption and the capillary condensationare influenced by the surface affinity of the porous matrix, which canbe tailored by a range of chemical modifications.

Thermal Modulation

For a single sensor, using thermal modulation, can help discriminatebetween different vapours. When the sensor working temperature ismodulated, the kinetics of the adsorption and reaction processes thatoccur on the sensor surface are altered. This leads to sensor responsethat is characteristic to species present, thus increased selectivity.

Porous Waveguide Sensing

Embodiments of the invention relate to the use of a porous waveguidewith sub-wavelengths features with a light source and detector tomeasure molecular absorption spectroscopy of species entering the poresof the waveguide. The porous waveguide can be made of any material andmay be fabricated in many different ways. Pore and nano-featuresdimensions are smaller than the wavelength of light, where Rayleighscattering losses (which vary as λ⁻⁴) are expected to be low enough toallow light to propagate in the waveguide. The preferred waveguidedesign we describe facilitates easy access of analytes into the pores(by contrast with ‘buried’ waveguides made of porous silicon). Thedetection optionally employs the capillary condensation phenomenon tofacilitate further discrimination of analytes that enter the pores.

Current optical (bio-)sensors are limited in their sensitivity becausethe chemical interactions are limited to the surface of the waveguidingdevice, while the high-intensity propagating mode is localised in thecore. Increasing the interaction between the propagating light and thetarget molecules, as well as increasing the surface area, results inincreased sensitivity and better SNR.

In FIG. 1, three different types of waveguides are compared. FIG. 1ashows a conventional waveguide where the light propagates in the coreand only the evanescent field interacts with the molecules of interest(dots). One way to improve the sensitivity is to add a small slot insidethe core (FIG. 1b ). This slot is very thin (smaller than the wavelengthof light) in order for the mode to propagate ‘normally’ in thestructure. This adds to the complexity of fabrication, and also the slotis limited in the number of molecules that it can accommodate. A porouswaveguide (FIG. 1c ) comprises many small pores, with the ability toaccommodate large quantity of molecules. The target molecules areabsorbed within the waveguide core, thus providing very sensitivedetection. Due to the small size of the pores (much smaller than thewavelength of light), the light can propagate in the porous core in asimilar manner to a conventional waveguide.

In addition to the large surface area which is generally desirable by asensor, the porous network offers additional advantages: The size of thepores can be tuned. This can provide physical discrimination based onsize—for example only the smaller molecules may be measured. The surfacemay be treated to become hydrophilic, hydrophobic or may be tailored bya range of chemical modifications. The surface may be functionalizedwith receptors to allow specific binding with the target molecules (DNA,antibody).

In the gas phase, the nanostructured optical waveguide significantlyincreases the sensitivity of detection for volatile organic compounds(VOCs) due to a capillary condensation phenomenon: Capillarycondensation is the physical tendency for a vapour to condense in asmall pore at temperatures well above the dew point (as described by theKelvin equation). During the capillary-condensation process, the air inthe voids is replaced by condensed vapour. The extent of thecondensation is influenced by the surface affinity of the porous matrixto the vapour molecules and depends on the vapour intrinsic properties.The molecules in the liquid are in equilibrium with the gaseousmolecules, and the process is reversible: as the gas concentrationdecreases, the molecules leave the pores. The nanostructured opticalwaveguide acts as a condenser or concentrator of organic volatiles. FIG.2 is a schematic illustration showing the role of the nanostructuredwaveguide: Conventionally, the light interacts with gas molecules whichare dispersed in air. However when a nano-porous waveguide isintroduced, the gas molecules condense inside the waveguide, providing asignificantly larger effective interaction length.

The dynamic curves of adsorption, condensation and desorption aredifferent for different vapours. FIG. 3 shows the real-time sensorresponse for 5 injections of two different vapours. The adsorption anddesorption of vapour into and out of the porous structure is fast andfully reversible (albeit with some hysteresis).

We now describe some further methods of improving the reliability andthe selectivity of this approach: Temperature modulation providesfurther discrimination—the capillary condensation and thus the dynamiccurves are different for different vapours. A waveguide array, inparticular an array of waveguides having different pore sizes and/orsurface treatment or surface functionalization facilitatesdiscrimination between target analytes. These techniques facilitatediscrimination based on analyte size and/or mass and/or boiling point,and discrimination between structural isomers and functional groups.

Initial feasibility tests were successfully conducted using thestructure of FIG. 4, which illustrates a fabricated waveguide. To makethe waveguide samples were prepared using p-type doped siliconsubstrates with a resistivity of 0.01 Ω-cm and (100) crystalorientation. The grooves (1.2 μm high and 70 μm wide) for the waveguideswere etched using standard lithographic process, and then the pores wereetched electrochemically using an electrolyte solution containing 30% HF(48% aqueous) and 70% ethanol. The thickness of the core and claddinglayers were 3 μm each. As the refractive index is determined by theapplied current density, it is possible to design multi-layeredstructures and graded-index planar waveguides in which the porosity isvaried through the vertical cross section of the structure.

The structure of an example resulting waveguide is shown in FIG. 4a ,with the top view and the cross-section morphology of porous silicon.The upper core is a low porosity layer and the cladding is a highporosity layer. Alternatively a waveguide may be fabricated with anextended low porosity layer with a raised optical (core) region in whichlight propagates, as illustrated in FIG. 4 b.

FIGS. 5a and 5b show a vertical cross-section (end-on) view of awaveguide array fabricated in this manner. FIG. 5a shows light comingout of a second waveguide of the array; FIG. 5b shows light coming outof a third waveguide of the array. FIG. 5c shows a view from above oflight propagation in one of the waveguides of the array.

FIG. 6 shows an experimental setup used to carry out near-IRmeasurements with the porous silicon waveguide. A small tube carryingsaturated vapours of different solvents (pentane, methanol, acetone andisopropyl alcohol) was placed above the waveguide in open air. Theoptical spectrum was then immediately recorded. The measured spectra areshown in FIG. 7.

As-prepared porous silicon is optically transparent from about 1 μm. Tofacilitate use in the visible, thermal oxidation can be employed totransforms silicon to silica, resulting in porous silica waveguideswhich are transparent at visible wavelengths and up to about 2.5 μm.

In embodiments of the invention the pore size of the waveguide coretypically has a size in the range 5 nm-30 nm. More generally, however,the pore size may lie in a range of from <1 nm up to a size that issmaller than the wavelength used, for example up to 500 nm.

The pore size is preferably measured at the surface of the core of thewaveguide for example by AFM (atomic force microscopy) or SEM. This isbecause in embodiments the pores do not have a well-defined size withinthe bulk of the material (FIG. 4).

The pore size of an individual pore may thus be taken as the averagediameter of a pore or the average width of the pore (for non-sphericalpores). The pore size of all pores will have a range or distribution ofvalues; the pore size may be taken as the peak of this distribution (themode of the pore size).

Other methods to measure porosity and pore size distribution include gasadsorption isotherms of N2 or CO2 at low temperatures. From those, theporosity and pore sizes may be calculated (indirectly), with someassumptions. For example, a pore size distribution may be calculatedusing the BJH (Barrett-Joyner-Halenda) method, which determines a poresize distribution based on a model of the adsorbent as a collection ofcylindrical pores (Barrett, E. P.; L. G. Joyner, P. P. Halenda (1951),“The Determination of Pore Volume and Area Distributions in PorousSubstances—Computations from Nitrogen Isotherms”. J. Am. Chem. Soc. 73(1): 373-380).

Alternatively, however, the porosity (proportion of total pore volume ina material) may be used as a proxy for pore size. This may be determinedusing a gravimetric method, as described in “Porous Silicon inPractice”, Prof. Michael J Sailor, Wiley-VCH, 2012, at page 134. Broadlyspeaking, this etches away a known volume of silicon, weighs the siliconbefore and after, and calculates the actual volume of silicon removedfrom the density of silicon, giving the percentage porosity. In somepreferred embodiments of the techniques we describe the porosity of thewaveguide core may be in the range 10% to 90% porosity, preferably thewaveguide core has >40% porosity (the cladding, where present has ahigher porosity than the core).

FIG. 8a shows an analyte sensing system 800 according to an embodimentof the invention. The system comprises an optical source 1 such as anLED, laser or lamp coupled to an optical fibre 2 and optional filter 2 ato provide an optical input to a porous waveguide sensor 3 as previouslydescribed. Light output from porous waveguide 3 optionally passesthrough a second filter 4 a into a second optical fibre 4 to an opticaldetector 5 such as a photodetector or spectrometer. The signal outputfrom detector 5 provides an input to a signal processor 6 such as asuitably programmed general purpose computer or dedicated signalprocessing circuitry.

Referring now to FIG. 8b , this shows a second analyte sensing system810, similar to that of FIG. 8a , in which optical fibres 2 and 4 areomitted. The optional filter 2 a and optional filter 4 a may comprise anarrow passband optical filter such as an interference filter or amultiple passband filter, for example aligned to one or more absorptionpeaks of a target analyte.

FIG. 8c shows a waveguide array analyte sensor 830 in which likeelements to those previously described are indicated by like referencenumerals. Thus the sensor system 830 comprises an optical spatialmultiplexer 7 to distribute light from source 1 into each of a pluralityof waveguides 3 arranged as a waveguide array 832. In FIG. 8c theoutputs of waveguides 3 are combined, optionally by an optical combiner(not shown). As illustrated in the variant waveguide array sensor system840 of FIG. 8d , one or both of the optical source(s) one and opticaldetector(s) 5 may be replaced by a plurality of sources/detectors ratherthan multiplexed.

FIG. 9 illustrates a temperature controlled porous waveguide 900 for usein any of the sensor systems of FIG. 8. The porous waveguide 900comprises a substrate 32 bearing a porous waveguide 31, for examplecomprising a core layer over a lower refractive index cladding layer. Aheating element 33 is provided under substrate 32, for examplecomprising a heating element and/or Peltier effect device, preferablywith a temperature sensor for closed loop temperature control ofsubstrate 32 and waveguide 31.

FIG. 10 shows an embodiment of a sensor probe 10 comprising a porouswaveguide sensor 3 as previously described. Fibre optic connections 2, 4provide respective input and output connections for the porous waveguidesensor, and these are respectively coupled to a remote optical source 1and to a remote optical detector 5.

Thus, broadly speaking we have described a sensor device for measuringmolecular absorption or Raman spectroscopy of analytes, the devicecomprising a light source, a porous waveguide and a detector. Heremolecular spectroscopy refers particularly to UV, near-IR, mid-IR andfar-IR absorption bands of analytes that enter into (are absorbed by)the material of which the porous waveguide is fabricated.

In embodiments the porous waveguide may be made of silicon, silica,alumina, chalcogenide, titanium dioxide or other materials that aretransparent or partially transparent in the desired optical range.Typical dimensions for the porous waveguide have width and height on amicrometre scale, a length in millimetres, and the inner, pore featuressmaller than the wavelength of light.

The light source used may provide one or more wavelengths in the rangeof UV, near-IR, mid-IR and far-IR. The source may be either a broadlight source or provide a one or more specific wavelengths. The detectormay be, for example, a spectrometer or a photodetector with or withoutan optical filter. Where used, a filter can be put at the light sourceand/or at the detector.

Optionally the external and/or internal surface of the porous waveguide(i.e. the outer face and/or the surface within the pores) may bechemically treated to be either hydrophilic, hydrophobic orfunctionalised with various chemical groups. Thus the surface may befunctionalised with receptor molecules such as DNA, protein, or antibodymolecules.

Embodiments of the sensor may be used to sense an analyte in either thegas or liquid phase.

In the gas phase, different vapour-phase materials, for example VOCs(volatile organic compounds), will condense differently inside the pores(according to the Kelvin equation). The adsorption and desorption of thegases into and from the pores, may be monitored in real-time to providetime-dependent information.

The diffusion of analyte into the core, retention of analyte within thecore, and analyte condensation is temperature-sensitive. Thereforeembodiments comprise a heater plate attached, for example, to the backside of the waveguide. By controlling the temperature one can tune whichanalytes, for example VOCs, will condense inside the pores, and whichwill not (or at least which preferentially condense/do not condense).Optionally temperature modulation may be employed in order to obtain atime-dependent temperature data for further discrimination.

Embodiments of the sensor system may in particular be used to measuregaseous analytes emitted from breath, urine or other biological/humansolids, bodily fluids or vapours.

The sensor or a similar device may also be used to ‘hold’ analyte as acondensed vapour—by allowing the analyte to enter the core and thenlowering the temperature to condense the analyte. The “stored” gas(vapour) may be released by increasing the temperature.

In addition to the light transmission through the waveguide, embodimentsof the sensor system also (optionally simultaneously) monitor the changein the refractive index of the waveguide, for example via white lightreflection.

Additionally or alternatively one or more dc or ac electrical propertiesof the sensor (waveguide) core may also be monitored, for exampleresistivity/conductance, and/or impedance. For example a pair ofelectrodes may be located on (along) the low porosity or core part ofthe waveguide and connected to an electrical characterisationdevice/system, for example for measuring resistance, impedance and/ordielectric constant. In a device of the type shown in FIG. 4b theelectrodes may be located alongside the core on the low porositymaterial, for ease of fabrication.

Such refractive index/electrical data may be used forsensing/discriminating between analytes.

Optionally the device may have one or more waveguides in parallel. Inembodiments each waveguide has different surface chemistry, porosity,temperature, and/or other features. This arrangement can improve thesensitivity/selectivity of the sensor system, by combining the data fromthe sensor array.

Embodiments of the waveguide may be fabricated in many ways. For exampleporous silicon may be produced by electrochemical etching. Optionally aporous silicon waveguide layer (core and optional cladding layer) may beremoved from the substrate after fabrication and placed on a substrateother than silicon.

In another method nanoparticles are deposited on a substrate to create aporous layer. In addition there are many methods which may be employedto exist to produce a porous material using a sol-gel process.Optionally one or more sensitising/functionalisingmolecules/nanoparticles may be incorporated inside the porous media.These may be employed to tune the optical and/or chemical properties forsensing. Optionally a gain material (a material for providing opticalgain) may be incorporated within the waveguide, either distributedwithin the waveguide or in one or more discrete regions.

No doubt many other effective alternatives will occur to the skilledperson. It will be understood that the invention is not limited to thedescribed embodiments and encompasses modifications apparent to thoseskilled in the art lying within the spirit and scope of the claimsappended hereto.

1. A method of selectively detecting the presence of an analyte, themethod comprising: providing at least one waveguide, the waveguidehaving a core comprising porous material; absorbing an analyte sampleinto said porous material of said core such that said analyte sample isheld within pores of said core; waveguiding radiation along said atleast one waveguide to an output to provide output radiation; measuringone or more spectral features of said absorbed analyte sample in saidoutput radiation due to absorption or scattering of said waveguidedradiation by said absorbed analyte sample; selectively identifying thepresence of a target analyte in said analyte sample from said one ormore spectral features; wherein molecular absorption or Ramanspectroscopy is performed on said analyte sample.
 2. A method as claimedin claim 1 wherein said one or more spectral features are enhanced bycapillary condensation.
 3. A method as claimed in claim 1 furthercomprising providing a plurality of waveguide core regions with aplurality of different physical and/or chemical modifications to saidcore, wherein said plurality of waveguide core regions comprise one orboth of a plurality of core regions of a plurality of said waveguidesand a plurality of core regions of a plurality of portions of said atleast one waveguide; waveguiding radiation through said plurality ofwaveguide core regions; measuring one or more said spectral features foreach of said differently modified core regions; and selectivelyidentifying said target analyte from a combination of said spectralfeatures for said differently modified core regions.
 4. A method asclaimed in claim 3 wherein said differently modified core regions havepores with size distributions having peaks at different pore sizes.
 5. Amethod as claimed in claim 3 or wherein said differently modified onregions comprise different functionalisations of said core material. 6.A method as claimed in claim 3, wherein said selective identifying usesa multi-component analysis of said combination of spectral features. 7.A method as claimed in claim 1 further comprising operating at aplurality of temperatures of said at least one waveguide, and measuringsaid one or more spectral features at said plurality of temperatures;wherein said selective identifying is responsive to said one or morespectral features at said plurality of temperatures.
 8. A method asclaimed in claim 7 wherein said temperatures are selected to change adegree of vapour condensation of said target analyte within said poresof said core.
 9. A method as claimed in claim 1 wherein said measuringcomprises waveguiding multiband radiation along said waveguide andmeasuring a spectrum of said output radiation.
 10. A method as claimedin claim 1 wherein said pores have a size distribution with a peak atless than 500 nm.
 11. A method as claimed in claim 1 comprisingproviding said waveguide on substrate and using porous silicon or poroussilica for said core.
 12. An analyte sensor, the sensor comprising: asubstrate bearing a waveguide, the waveguide comprising: a first,cladding layer on said substrate; a second, core layer, comprisingporous material, over said cladding layer; a radiation source to provideradiation into said waveguide; a radiation detector to detect radiationwhich has been waveguided along said waveguide; and a signal processor,coupled to said radiation detector, to identify the presence of a targetanalyte absorbed within said core layer from one or more spectralfeatures of said detected radiation due to absorption or scattering ofsaid waveguided radiation by said absorbed target analyte.
 13. Ananalyte sensor as claimed in claim 12 wherein said core layer and saidcladding layer each comprise a porous silicon-based material.
 14. Amethod of fabricating an analyte sensor waveguide as claimed in claim13, the method comprising: providing a silicon substrate; supplying afirst current at a first current density perpendicular to saidsubstrate; performing a first etch of said substrate to fabricate saidcore layer; and supplying a second current at a second density slowlyperpendicular to said substrate; performing a second etch of saidsubstrate to fabricate said core layer.
 15. A method of fabricating ananalyte sensor, comprising fabricating a waveguide as claimed in claimed14, and then fabricating said analyte sensor using said waveguide. 16.Apparatus for selectively detecting the presence of an analyte, theapparatus comprising: at least one waveguide, the waveguide having acore comprising porous material; a radiation source to provide radiationinto said waveguide; a radiation detector to detect radiation which hasbeen waveguided along said waveguide; and a signal processor, coupled tosaid radiation detector, to identify the presence of a target analyteabsorbed within said core layer from one or more spectral features ofsaid target analyte in said detected radiation due to absorption orscattering of said waveguided radiation by said absorbed target analyte.17. Apparatus as claimed in claim 16 comprising a plurality of waveguidecore regions with a plurality of different physical and/or chemicalmodifications to said core; wherein said plurality of waveguide coreregions comprise one or both of a plurality of core regions of aplurality of said waveguides and a plurality of core regions of aplurality of portions of said at least one waveguide.
 18. A method asclaimed in claim 17 wherein said signal processor is configured toselectively identify said target analyte from a combination of saidspectral features for said differently modified core regions.
 19. Amethod as claimed in claim 16, further comprising a temperaturecontroller to control a temperature of said at least one waveguide to aplurality of different temperatures; and wherein said signal processoris configured to selectively identify said target analyte by measuringsaid one or more spectral features at said plurality of differenttemperatures.
 20. A method of analysing a bodily fluid sample using themethod of claim
 1. 21. Apparatus as claimed in claim 16 for analysing abodily fluid sample, the apparatus further comprising a bodily fluidsample holder, and means to selectively allow passage of bodily fluidvapour from the sample holder for analysis.